Fate of Embryonic Stem Cells Transplanted into the Deafened Mammalian Cochlea

Abstract

Spiral ganglion neurons (SGNs), the primary afferent neurons of the cochlea, degenerate following a sensorineural hearing loss (SNHL) due to lack of trophic support normally received from hair cells. Cell transplantation is emerging as a potential strategy for inner ear rehabilitation, as injected cells may be able to replace damaged SGNs in the deafened cochlea. An increase in the number of surviving SGNs may result in improved efficacy of cochlear implants (CIs). We examined the survival of partially differentiated mouse embryonic stem cells (MESCs), following xenograft transplantation into the deafened guinea pig cochlea (n = 15). Cells were delivered directly into the left scala tympani via microinjection through the round window. Small numbers of MESCs were detected in the scala tympani for up to 4 weeks following transplantation and a proportion of these cells retained expression of neurofilament protein 68 kDa in vivo. While this delivery method requires refinement for effective long-term replacement of damaged SGNs, small numbers of MESCs were capable of survival in the deafened mammalian cochlea for up to 4 weeks, without causing an inflammatory tissue response.

Transplantation of Mouse Embryonic Stem Cells into the Cochlea of an Auditory-Neuropathy Animal Model: Effects of Timing after Injury

“…Numerous groups have reported variable success rates of cell delivery using various deafened animal models (Hu et al 2004Regala et al 2005;Okano et al 2005;Sekiya et al 2006;Corrales et al 2006;Coleman et al 2006). Among these studies, the surgical approaches used for stem cell delivery can be divided into two general categories based on the sites of injection.…”

“…The great advantage of the scala tympani approach is minimal trauma to the cochlea. However, the surviving cells are scattered throughout the cochlea and vestibular compartments with a relatively small number of cells migrating into RC (Hu et al 2004Coleman et al 2006). Approaches for introducing cells into the auditory nerve have shown better outcomes of transplanted cells.…”

“…Potential cell sources for inner ear transplantation include fetal dorsal root ganglion cells (Hu et al 2004;Regala et al 2005), neural progenitor cells (Ito et al 2001;Corrales et al 2006;), stem or progenitor cells isolated from inner ear (Li et al 2003a;Doetzlhofer et al 2004;Rask-Andersen et al 2005;Zhai et al 2005), immortalized auditory neuroblast cells (Nicholl et al 2005;Liu et al 2006a, b), ESCs and their derived neuronal cells (Li et al 2003b;Hu et al 2004Hu et al , 2005Hildebrand et al 2006;Okano et al 2005;Regala et al 2005;Coleman et al 2006;Sakamoto et al 2004;Sekiya et al 2006;Corrales et al 2006), and marrow stromal cells treated with sonic hedgehog and retinoic acid (Kondo et al 2005). ESCs derived from the inner cell mass of the blastocyst are capable of undergoing an unlimited number of divisions and differentiating into cell types of all three germ layers.…”

Stem cell transplantation for auditory nerve replacement

“…They also found the majority had differentiation into a glial phenotype, based on GFAP immunostaining and only a small percentage reached a neuronal type phenotype. Coleman et al (2006) placed mouse embryonic stem cells (mESCs) into guinea pig cochlea and found poor survival, with 4-6 mESCs per profile through scala tympani and 1 per profile through Rosenthal's canal, with a significant decline in the number in scala tympani between 2 and 4 weeks following placement. A portion of the surviving mESCs (not specified in the text) showed a neuronal phenotype based on neurofilament immunolabeling.…”

“…Coleman et al., (2006) implanted B-5 mESCs into guinea pig cochlea and found moderate survival with most differentiated into a glial phenotype. We used the same B-5 cell line of undifferentiated mESCs and added intrascalar application of the neurotrophic factor (NTF) glial cell line derived neurotrophic factor (GDNF) following the mESC placement into guinea pig cochlea.…”